Stirred-tank reactor system

• US 20050239198A1
• Filed: 02/22/2005
• Published: 10/27/2005
• Est. Priority Date: 04/27/2004
• Status: Abandoned Application

• Current Assignee: Baxalta GmbH (Shire plc), Baxalta Incorporated (Shire plc)
• Original Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Inventors: Kunas, Kurt T., Oakley, Robert V.
• Application Number:
  US11/064,252
• Publication Number:
  US 20050239198A1
• Time in Patent Office: Days
• US Class Current: 435/297.100
• CPC Class Codes: B01F 2101/44 Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
• CPC Class Codes: B01F 27/071 Fixing of the stirrer to the shaft
• CPC Class Codes: B01F 27/88 with a separate receptacle-stirrer unit that is adapted to be coupled to a drive mechanism
• CPC Class Codes: B01F 27/91 with propellers
• CPC Class Codes: B01F 33/86 Mixing heads comprising a driven stirrer
• CPC Class Codes: B01F 35/51 characterised by their material
• CPC Class Codes: B01F 35/513 Flexible receptacles, e.g. bags supported by rigid containers
• CPC Class Codes: C12M 23/00 Constructional details, e.g. recesses, hinges flow directing inserts in C12M27/18-C12M27/24; apparatus for chemical or physical processes in general B01J, chemical or physical laboratory apparatus in general B01L
• CPC Class Codes: C12M 23/06 Tubular C12M23/08, C12M23/16 take precedence
• CPC Class Codes: C12M 23/14 Bags
• CPC Class Codes: C12M 23/26 flexible flexible containers for laboratory use B01L3/505
• CPC Class Codes: C12M 23/28 disposable or single use
• CPC Class Codes: C12M 27/02 Stirrer or mobile mixing elements
• CPC Class Codes: C12M 29/06 Nozzles; Sprayers; Spargers; Diffusers per se B01F23/231, B01J19/26
• CPC Class Codes: C12M 41/00 Means for regulation, monitoring, measurement or control, e.g. flow regulation controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

The present invention relates to a stirred-tank reactor system and methods of preparing such systems. The present invention further encompasses the use of the stirred-tank reactor system as a disposable bioreactor and in kits with disposable elements.

Claims

1. A stirred-tank reactor system, comprising:

(i) a flexible bag with at least one opening, wherein the bag functions as a sterile container for a fluidic medium;

(ii) a shaft situated within the bag;

(iii) an impeller attachable to said shaft, wherein said impeller is used to agitate the fluidic medium to provide a hydrodynamic environment; and

(iv) a bearing attached to said shaft and to said opening of the bag.

2. The stirred-tank system of claim 1, wherein said system is disposable.

3. The stirred-tank system of claim 1, wherein said system is pre-sterilized.

4. The stirred-tank reactor system of claim 1, wherein said system further comprises a housing on the outside of the bag, wherein said housing includes at least one support that holds the bearing and a motor, and wherein said bag is contained within the housing.

5. The stirred-tank reactor system of claim 4, wherein said system further includes a heater selected from the group consisting of a heating pad, a steam jacket, and a circulating fluid or water heater.

6. The stirred-tank reactor system of claim 5, wherein said heater is located between the bag and the housing.

7. The stirred-tank reactor system of claim 5, wherein said heater is incorporated into the housing.

8. The stirred-tank reactor system of claim 4, wherein the housing further includes a plurality of baffles and the bag folds around the baffles.

9. The stirred-tank reactor system of claim 4, wherein said system further includes a product loop with flow past a pH sensor and a dissolved-oxygen sensor, wherein said sensors are incorporated into the housing.

10. The stirred-tank reactor system of claim 4, wherein said housing is selected from the group consisting of a metal barrel, a plastic barrel, wood barrel, and a glass barrel.

11. The stirred-tank reactor system of claim 1, wherein said bag is a disposable, plastic bag.

12. The stirred-tank reactor system of claim 1, wherein said fluidic medium is selected from the group consisting of a biological fluid, a cell culture medium, a culture of microorganisms, and a food production.

13. The stirred-tank reactor system of claim 12, wherein the fluidic medium is a cell culture medium and the system is operated in batch mode, semi-batch mode, fed-batch mode, or continuous mode.

14. The stirred-tank reactor system of claim 1, wherein said impeller agitates the fluidic medium by stirring.

15. The stirred-tank reactor system of claim 14, wherein said impeller is selected from the group consisting of Rushton, hydrofoil, pitched blade, and marine.

16. The stirred-tank reactor system of claim 1, wherein said bag is affixed to the shaft and the bearing through at least one seal or o-ring such that the inside of the bag remains sterile.

17. The stirred-tank reactor system of claim 16, wherein said seals or o-rings are affixed to the bag.

18. The stirred-tank reactor system of claim 16, wherein said bag further includes a pH sensor and a dissolved-oxygen sensor, wherein said sensors are incorporated into the bag.

19. The stirred-tank reactor system of claim 16, wherein said system further includes at least one internal pouch sealed to the bag, wherein the pouch includes one end that can be opened to the outside of the bag such that a probe can be inserted into the reactor.

20. The stirred-tank reactor system of claim 19, wherein said probe is selected from the group consisting of a temperature probe, a pH probe, a dissolved gas sensor, an oxygen sensor, a carbon dioxide sensor, a cell mass sensor, a nutrient sensor, and an osmometer.

21. The stirred-tank reactor system of claim 16, wherein said system further includes a least one port in the bag allowing for the connection of a device to the port, wherein said device is selected from the group consisting of a tube, a filter, a sampler, a probe and a connector.

22. The stirred-tank reactor system of claim 21, wherein the port allows for gas flow in and out of the bag.

23. The stirred-tank reactor system of claim 21, wherein the port allows for media flow in and out of the bag.

24. The stirred-tank reactor system of claim 21, wherein the port allows for sampling, inoculation, titration, adding of chemostat reagents, and sparging.

29. A kit comprising:

(i) the stirred-tank reactor system of claim 16;

and

(ii) instructions for use.

30. The kit of claim 29, wherein said stirred-tank reactor system is disposable.

31. The kit of claim 29, wherein said stirred-tank reactor system includes at least one disposable element selected from the group consisting of the bag, the shaft, the impeller, and the bearing.

32. The kit of claim 29, wherein said bag is affixed to the shaft and the bearing through at least one seal or o-ring such that the inside of the bag remains sterile.

33. The kit of claim 29, wherein said bag further includes a pH sensor and a dissolved-oxygen sensor, wherein said sensors are incorporated into the bag.

34. The kit of claim 29, wherein said system further includes at least one internal pouch sealed to the bag, wherein the pouch includes one end that can be opened to the outside of the bag such that a probe can be inserted into the reactor.

35. The kit of claim 34, wherein said probe is selected from the group consisting of a temperature probe, a pH probe, a dissolved gas sensor, an oxygen sensor, a carbon dioxide sensor, a cell mass sensor, a nutrient sensor and an osmometer.

36. The kit of claim 29, wherein said system further includes a least one port in the bag allowing for the connection of a device to the port, wherein said device is selected from the group consisting of a tube, a filter, a sampler, a probe and a connector.

37. The kit of claim 36, wherein the port allows for gas flow in and out of the bag.

38. The kit of claim 36, wherein the port allows for media flow in and out of the bag.

39. The kit of claim 36, wherein the port allows for sampling, inoculation, titration, adding of chemostat reagents, and sparging.

40. A bag for use in the stirred-tank reactor system of claim 1.

41. The bag of claim 40, wherein said bag is a disposable plastic bag.

42. The bag of claim 40, wherein said bag further includes at least one disposable element selected from the group consisting of a seal, an o-ring, a port, a pouch, a tube, a filter, a sampler, a probe, a sensor and a connector.

25. A method for preparing a stirred-tank reactor system, comprising:

(i) providing a flexible bag with at least one opening, wherein the bag functions as a sterile container for a fluidic medium;

(ii) inserting a shaft with an impeller attachable to said shaft into the bag, wherein said impeller is used to agitate the fluidic medium to provide a hydrodynamic environment;

(iii) attaching a bearing to said shaft and to said opening of the bag; and

(iv) sealing the bag to the shaft and the bearing such that the inside of the bag remains sterile.

26. The method of claim 25, wherein said stirred-tank reactor system is pre-sterilized.

27. The method of claim 25, wherein said stirred-tank reactor system is disposable.

28. The method of claim 25, wherein said stirred-tank reactor system includes at least one disposable element selected from the group consisting of the bag, the shaft, the impeller, and the bearing.